The primary objective of the DRTC Mouse Models Core is to create a shared resource for the establishment, maintenance and experimentation on mouse models of type 1 and type 2 diabetes and related disorders to assist DRTC investigators in meeting their research objectives. Specific aims of the core are: 1.Produce transgenic mice in standard laboratory strains; 2. Produce transgenic mice in the NOD mouse background; 3. Produce transgenic mice carrying bacterial artificial chromosomes (BACs), in standard and NOD backgrounds; 4. Provide standardized ES cells and assistance with producing gene targeted clones; 5. Establish gene-targeting procedures for targeting the NOD chromosomes in embryonic stem (ES) stern cell lines derived from NOD x 129 F1 mice, facilitating the generation of gene knockout and knock-in mice that can be rapidly inbred to homozygosity in NOD; 6. Produce gene targeted mice via blastocyst injection of standard and NOD ES cell clones; and 7. Provide liaison to the Stanford University Gene Trap Resource, facilitating the screening by DTRC members for mouse insertional mutations with phenotypes relevant to types I and II diabetes. To meet these aims, the core will operate in a fashion similar to most institutional transgenic and targeted mutagenesis cores. This facility will, however, emphasize and specifically support diabetes-related projects. For example, the core will establish routine microinjection and gene-targeting procedures using zygotes and embryonic stem (ES) cell lines from the NOD (and potentially other) mouse strains that are of key significance for diabetes research. The Core will import and maintain relevant mouse strains and ES cell lines relevant in diabetes research and it will establish the capability to derive new ES lines to complement external sources. In addition, the Core will subscribe to a regional consortium that is producing new mutations in the mouse through 'gene-trap' insertion technologies, so as to identify new mutant mice showing developmental or physiological phenotypes relevant to research of the UCSF DRTC in types I and II diabetes. A major focus of the core will be on establishing the capability to genetically manipulate the non-obese diabetic (NOD) mouse via transgenic and gene targeting experiments.